Wright was right: leveraging old data and new methods to illustrate the critical role of epistasis in genetics and evolution.

Much of evolutionary theory is predicated on assumptions about the relative importance of simple additive versus complex epistatic genetic architectures. Previous work suggests traits strongly associated with fitness will lack additive genetic variation, whereas traits less strongly associated with fitness are expected to exhibit more additive genetic variation. We use a quantitative genetics method, line cross analysis, to infer genetic architectures that contribute to trait divergence. By parsing over 1,600 datasets by trait type, clade, and cross divergence, we estimated the relative importance of epistasis across the tree of life. In our comparison between life-history traits and morphological traits, we found greater epistatic contributions to life-history traits. Our comparison between plants and animals showed that animals have more epistatic contribution to trait divergence than plants. In our comparison of within-species versus between-species crosses, we found that only animals exhibit a greater epistatic contribution to trait divergence as divergence increases. While many scientists have argued that epistasis is ultimately of little importance, our results show that epistasis underlies much of trait divergence and must be accounted for in theory and practical applications like domestication, conservation breeding design, and understanding complex diseases.

Specialized metabolism by trichome-enriched Rubisco and fatty acid synthase components.

Acylsugars, specialized metabolites with defense activities, are secreted by trichomes of many solanaceous plants. Several acylsugar metabolic genes (AMGs) remain unknown. We previously reported multiple candidate AMGs. Here, using multiple approaches, we characterized additional AMGs. First, we identified differentially expressed genes between high- and low-acylsugar-producing F2 plants derived from a cross between cultivated tomato (Solanum lycopersicum) and a wild relative (Solanum pennellii), which produce acylsugars that are ∼1% and ∼20% of leaf dry weight, respectively. Expression levels of many known and candidate AMGs positively correlated with acylsugar amounts in F2 individuals. Next, we identified lycopersicum-pennellii putative orthologs with higher nonsynonymous to synonymous substitutions. These analyses identified four candidate genes, three of which showed enriched expression in stem trichomes compared to underlying tissues (shaved stems). Virus-induced gene silencing confirmed two candidates, Sopen05g009610 [beta-ketoacyl-(acyl-carrier-protein) reductase; fatty acid synthase component] and Sopen07g006810 (Rubisco small subunit), as AMGs. Phylogenetic analysis indicated that Sopen05g009610 is distinct from specialized metabolic cytosolic reductases but closely related to two capsaicinoid biosynthetic reductases, suggesting evolutionary relationship between acylsugar and capsaicinoid biosynthesis. Analysis of publicly available datasets revealed enriched expression of Sopen05g009610 orthologs in trichomes of several acylsugar-producing species. Similarly, orthologs of Sopen07g006810 were identified as solanaceous trichome-enriched members, which form a phylogenetic clade distinct from those of mesophyll-expressed "regular" Rubisco small subunits. Furthermore, δ13C analyses indicated recycling of metabolic CO2 into acylsugars by Sopen07g006810 and showed how trichomes support high levels of specialized metabolite production. These findings have implications for genetic manipulation of trichome-specialized metabolism in solanaceous crops.

A treated case of rhinocerebral zygomycosis with aspergillosis: a case report from India.

Zygomycosis and aspergillosis are two serious fungal infections that are commonly seen in immunocompromised patients. Since both of these infections involve fungi that invade vessels of the arterial system, an early and rapid diagnosis by direct examination of KOH mounts of the relevant clinical sample can clinch the diagnosis. Here, we present a case of a 60-year-old diabetic patient who presented with swelling and pain over the nose and left eye for 7 days with loss of vision in the left eye. After investigation, the patient was diagnosed as having rhinocerebral mucormycosis and aspergillosis, and was initially treated with amphotericin B (1 mg kg-1 day-1 intravenously), followed by endoscopic debridement under general anaesthesia. The patient gradually improved after surgery, and treatment with intravenous amphotericin B was continued along with the addition of 200 mg oral voriconazole twice daily (for the aspergillosis). With prompt diagnosis and treatment, the patient survived these fatal fungal co-infections and finally was discharged.

Candidate Gene Networks for Acylsugar Metabolism and Plant Defense in Wild Tomato Solanum pennellii.

Many solanaceous plants secrete acylsugars, which are branched-chain and straight-chain fatty acids esterified to Glu or Suc. These compounds have important roles in plant defense and potential commercial applications. However, several acylsugar metabolic genes remain unidentified, and little is known about regulation of this pathway. Comparative transcriptomics between low- and high-acylsugar-producing accessions of Solanum pennellii revealed that expression levels of known and novel candidate genes (putatively encoding beta-ketoacyl-(acyl-carrier-protein) synthases, peroxisomal acyl-activating enzymes, ATP binding cassette (ABC) transporters, and central carbon metabolic proteins) were positively correlated with acylsugar accumulation, except two genes previously reported to be involved in acylglucose biosynthesis. Genes putatively encoding oxylipin metabolic proteins, subtilisin-like proteases, and other antimicrobial defense proteins were upregulated in low-acylsugar-producing accessions. Transcriptome analysis after biochemical inhibition of biosynthesis of branched-chain amino acids (precursors to branched-chain fatty acids) by imazapyr showed concentration-dependent downregulation of known and most acylsugar candidate genes, but not defense genes. Weighted gene correlation network analysis identified separate coexpressed gene networks for acylsugar metabolism (including six transcription factor genes and flavonoid metabolic genes) and plant defense (including genes putatively encoding NB-ARC and leucine-rich repeat sequences, protein kinases and defense signaling proteins, and previously mentioned defense proteins). Additionally, virus-induced gene silencing of two trichomes preferentially expressed candidate genes for straight-chain fatty acid biosynthesis confirmed their role in acylsugar metabolism.

Expressing collective voices on children's health: photovoice exploration with mothers of young children from the Indian Sundarbans.

BACKGROUND: The Indian Sundarbans is marked by inhospitable terrain and frequent climatic shocks which jointly hinder access to health care. Community members, and women in particular, have few means to communicate their concerns to local decision makers. Photovoice is one way in which communities can raise their local health challenges with decision makers. This study unlocks mothers' voices on the determinants of their children's health to inform local level decision-making on child health issues in the Indian Sundarbans. METHODS: Photovoice action research was conducted in three blocks in the Sundarbans region of West Bengal, India. The project involved eight groups of eight to ten mothers who had at least one child below 6 years of age across four villages. The mothers received training on photo documentation and ethical concerns before taking two rounds of photographs within 6 months, interspersed by fortnightly group meetings facilitated by researchers. Photographs and key messages were communicated to local decision makers during block and village level interface sessions with the mothers and researchers. RESULTS: Mothers' photos focused on specific determinants of health, such as water and sanitation; health status, such as malnutrition and non-communicable diseases; service accessibility; climate conditions; and social issues such as early marriage and recurrent pregnancy. Some issues were not captured by photos but were discussed in group meetings, including domestic violence and the non-availability of medical practitioners. We found differences by mother's educational status, livelihood and caste identity in the extent and nature of photographs taken. As a result of the mother's interface with community decision makers, which included showcasing a selection of their photos, efforts to improve road infrastructure and human resource availability in the primary health centres and local government were realized. CONCLUSION: Photovoice has the potential to express the voices of vulnerable communities regarding their health needs and can help them dialogue with local decision makers to inform community health policy and planning. More needs to be done to understand how social differences among photovoice participants influences how they engage with the methodology.